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Eukaryotic Cell, May 2005, p. 981-990, Vol. 4, No. 5
1535-9778/05/$08.00+0     doi:10.1128/EC.4.5.981-990.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Class I Histone Deacetylase Thd1p Affects Nuclear Integrity in Tetrahymena thermophila

Emily A. Wiley,1,2,3* Tamara Myers,2 Kathryn Parker,2 Theodore Braun,1 and Meng-Chao Yao3*

W. M. Keck Joint Science Department, Claremont Colleges, Claremont, California 91711,1 Department of Biology, Mount Holyoke College, South Hadley, Massachussetts 01075,2 Fred Hutchinson Cancer Research Center, Seattle, Washington 981093

Received 3 December 2004/ Accepted 24 February 2005

Class I histone deacetylases (HDACs) participate in the regulation of DNA-templated processes such as transcription and replication. Members of this class can act locally at specific sites, or they can act more globally, contributing to a baseline acetylation state, both of which actions may be important for genome maintenance and organization. We previously identified a macronuclear-specific class I HDAC in Tetrahymena thermophila called Thd1p, which is expressed early in the development of the macronucleus when it initially becomes transcriptionally active. To test the idea that Thd1p is important for global chromatin integrity in an active macronucleus, Tetrahymena cells reduced in expression of Thd1p were generated. We observed phenotypes that indicated loss of chromatin integrity in the mutant cells, including DNA fragmentation and extrusion of chromatin from the macronucleus, variable macronuclear size and shape, enlarged nucleoli, and reduced phosphorylation of histone H1 from bulk chromatin. Macronuclei in mutant cells also contained more DNA. This observation suggests a role for Thd1p in the control of nuclear DNA content, a previously undescribed role for class I HDACs. Together, these phenotypes implicate Thd1p in the maintenance of macronuclear integrity in multiple ways, probably through site-specific changes in histone acetylation since no change in the acetylation levels of bulk histones was detected in mutant cells.


* Corresponding author. Mailing address for Emily A. Wiley: W. M. Keck Joint Science Department, Claremont Colleges, 925 N. Mills Ave., Claremont, CA 91711. Phone: (909) 607-9698. Fax: (909) 621-8588. E-mail: ewiley{at}jsd.claremont.edu. Present address for Meng-Chao Yao: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan. Phone: 886-2-2782-1436. E-mail: mcyao{at}imb.sinica.edu.tw.


Eukaryotic Cell, May 2005, p. 981-990, Vol. 4, No. 5
1535-9778/05/$08.00+0     doi:10.1128/EC.4.5.981-990.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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